Checkpoint genes are known to be involved in the maintenance of genomic integrity and their aberrant expression can lead to cancer. Paralogue of human HRad9 is called HRad9B. Gene product is structurally related to hRad9 protein (55% similar and 35% identical). HRad9B gene is expressed predominantly in the testis and found in decreased amount in testicular tumours, particularly seminomas (Hopkins et al., 2003).

Carboxy terminus of hRad9 contains a FXXLF motif which interrupts the androgen-induced interaction between the C and N terminus of androgen receptor (AR), acting as a co-regulator to suppress androgen-AR transactivation in prostrate cancer cells (Wang et al., 2004). This denotes a possible tumour suppressor function of hRad9. Recent study has confirmed that high levels of Rad9 expression is found in prostate cancer cells and the high protein levels in prostate adenocarcinomas were generally associated with more advanced disease (Zhu et al., 2008). Similar to previous findings in breast cancer (Cheng et al., 2005), the increased expression of Rad9 in prostate cancer cells was in part due to aberrant methylation or gene amplification (Zhu et al., 2008). The study failed to show that the role of Rad9 in prostate tumorigenesis was androgen dependent, since both androgen dependent CWR22 and LNCaP cell lines as well as androgen independent DU145 and PC-3 cell lines were found to contain high levels of Rad9 protein (Zhu et al., 2008).

Presence of hyperphosphorylated forms of hRad9 has been found in the nuclei of surgically resected primary lung carcinoma cells (Maniwa et al., 2005). No mutation of the hRad9 gene was found in lung cancer cells, but a nonsynonymous single nucleotide polymorphism (SNP), His239Arg was found in 8 out of 50 lung adenocarcinoma patients, suggesting a possible association of this SNP with the development of cancer (Maniwa et al., 2006).

Over-expression of hRad9 mRNA was found in breast cancer, which was shown to be correlated with tumour size (p = 0.037) and local recurrence (p = 0.033). Over-expression of Rad9 mRNA was partly due to increase in RAD9 gene amplification and aberrant DNA methylation at a putative Sp 1/3 binding site within the second intron of the RAD9 gene. Promoter assays indicate that the Sp 1/3 site in intron 2 may act as a silencer. Further experiments in silencing Rad9 expression by RNAi inhibit the proliferation of MCF-7 cell line in vitro. These findings suggested that Rad9 is a new oncogene candidate on Ch11q13 with a role in breast cancer progression (Cheng et al., 2005). In contrast to previous findings in testicular tumours, increased hRad9 protein was found in the nuclei of breast cancer cells. These were shown to exist as hyperphosphorylated forms, with molecular weights of 65 and 50 kDa. Since the theoretical molecular weight of hRad9 is 45 kDa (Lindsey-Boltz et al., 2001), these larger forms most likely represent hyperphosphorylated hRad9 and its hRad9-hRad1-hHus1 complex (Chan et al., 2008; St Onge et al., 1999). Localization of hyperphosphorylated forms of hRad in the nucleus of cancer cells is in keeping with its function in ameliorating DNA instability, whereby it inadvertently assists tumour growth.